In mice, furosemide-induced hepatotoxicity was often accompanied by impaired renal function. After small doses (50 mg/kg sc), urinary excretion of furosemide exceeded the biliary excretion. In mice the increase unaccounted for furosemide from 59-85% (35-58% dose), as the dose was increased probably represented metabolized furosemide. Decreases in urinary excretion of unchanged furosemide, low renal clearances, and reduced diuretic responses indicated that large doses of furosemide impaired renal function thereby decreasing the total body clearance of furosemide thereby decreasing the total body clearance of furosemide. At 30 minutes after the administration of furosemide, the ratio of the clearances of furosemide and creatinine were nearly independent of the dose. Thus, the decrease in furosemide clearance did not appear to be due solely to saturation of a renal transport system for furosemide. Treatment with Lactated Ringer's Injection, U.S.P., did not prevent impaired renal function, as measured by plasma urea nitrogen, and hepatic necrosis, as measured by plasma glutamic-pyruvic transaminase, after large doses of furosemide.